FBF1 deficiency promotes beiging and healthy expansion of white adipose tissue

Preadipocytes dynamically produce sensory cilia. However, the role of primary cilia in preadipocyte differentiation and adipose homeostasis remains poorly understood. We previously identified transition fiber component FBF1 as an essential player in controlling selective cilia import. Here, we establish Fbf1(tm1a/tm1a) mice and discover that Fbf1(tm1a/tm1a) mice develop severe obesity, but surprisingly, are not predisposed to adverse metabolic complications. Obese Fbf1(tm1a/tm1a) mice possess unexpectedly healthy white fat tissue characterized by spontaneous upregulated beiging, hyperplasia but not hypertrophy, and low inflammation along the lifetime. Mechanistically, FBF1 governs preadipocyte differentiation by constraining the beiging program through an AKAP9-dependent, cilia-regulated PKA signaling, while recruiting the BBS chaperonin to transition fibers to suppress the hedgehog signaling-dependent adipogenic program. Remarkably, obese Fbf1(tm1a/tm1a) mice further fed a high-fat diet are protected from diabetes and premature death. We reveal a central role for primary cilia in the fate determination of preadipocytes and the generation of metabolically healthy fat tissue.

Automated summary

Primary cilia play a central role in the determination of preadipocyte fate and the generation of metabolically healthy fat tissue by controlling transition fiber processes and signaling pathways, impacting adipocyte differentiation, obesity, and metabolic health.